Peptibase
Anti-Aging

FOXO4-DRI

Also known as: FOX04-DRI, FOXO4 D-Retro-Inverso, Proxofim

Preclinical
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Key Facts: FOXO4-DRI

Category
Anti-Aging
FDA Status
Not FDA Approved
Clinical Status
Preclinical - Extensive animal research, no human trials initiated yet
Administration
Subcutaneous injection (community), IV/IP in animal studies
Typical Dose
2-10 mg every other day for 3 doses (one cycle)
Frequency
3 doses every other day, 1-3 cycles per year
Duration
1 cycle = 3 doses over 5-6 days, repeat 1-3x yearly
Also Known As
FOX04-DRI, FOXO4 D-Retro-Inverso, Proxofim

Mechanism of Action

FOXO4-DRI is a D-retro-inverso peptide that interferes with the binding between FOXO4 and p53 proteins. In senescent cells, FOXO4 binds to p53 to prevent apoptosis, allowing these dysfunctional cells to persist. FOXO4-DRI competes for this binding, releasing p53 to trigger apoptosis specifically in senescent cells while sparing healthy cells.

Research Summary

Landmark 2017 Cell study demonstrated that FOXO4-DRI restored fitness, fur density, and renal function in aged mice. Studies show improved kidney tubular cell markers, better urea/creatinine metrics, and reduced SASP (senescence-associated secretory phenotype) cytokines. A 2025 Nature Communications study provided detailed structural insights into the FOXO4-p53 interaction mechanism. Cleara Biotech is developing FOXO4-DRI for conditions including kidney disease, COPD, and osteoarthritis.

Trial Progress:Phase I
Pre
I
II
III
IV
FDA

Dosing Information

Animal Studies·Primarily animal/preclinical research

Note: Animal study doses may not translate directly to humans.

Typical Dosingⓘ

Community experience

Common Dose

2-10 mg every other day for 3 doses (one cycle)

Range

2-25 mg per injection, 6-75 mg total per cycle

Frequency

3 doses every other day, 1-3 cycles per year

Senolytic peptide - used in short intermittent cycles, not daily. Mouse studies used 5 mg/kg x3 doses (translates to ~25 mg/dose for 60kg human). Biohacker protocols vary: some use 2-3 mg every other day for 6 days, others use higher 10-25 mg doses for 3 injections. Lower-dose protocols (300-500 mcg daily for weeks) also reported. Subcutaneous injection most common. Side effects may include injection site reactions, fatigue, muscle soreness, nausea.

Research Dosingⓘ

Scientific studies

Doses from animal studies and biohacker community protocols

Duration

1 cycle = 3 doses over 5-6 days, repeat 1-3x yearly

Administration

Subcutaneous injection (community), IV/IP in animal studies

Timing & Administration

Best Time to Take

Per research protocol

Intermittent dosing (e.g., 3 doses over 1 week, then break)

Food Recommendation

With or without food

Why This Timing?

FOXO4-DRI is typically administered in intermittent treatment cycles rather than daily dosing. The peptide triggers apoptosis in senescent cells, which then need time for clearance and tissue regeneration.

Possible Side Effects

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

  • ●Generally well-tolerated in animal studies
  • ●Injection site reactions (burning, itching)
  • ●Fatigue
  • ●Muscle soreness
  • ●Nausea
  • ●No significant effects on platelet levels or blood values in animal studies
  • ●No observed damage to non-proliferative tissues (heart)
  • ●Limited human safety data
  • ●Theoretical concern: could affect beneficial senescent cells (wound healing, tumor suppression)

References

Research This Peptide Further

PubMedClinicalTrials.govFDA.gov

Frequently Asked Questions

What does FOXO4-DRI do?

A senolytic peptide designed to selectively eliminate senescent 'zombie' cells by disrupting the FOXO4-p53 interaction. Shows promise for restoring tissue function in aging, including kidney health restoration.

How does FOXO4-DRI work?

FOXO4-DRI is a D-retro-inverso peptide that interferes with the binding between FOXO4 and p53 proteins. In senescent cells, FOXO4 binds to p53 to prevent apoptosis, allowing these dysfunctional cells to persist. FOXO4-DRI competes for this binding, releasing p53 to trigger apoptosis specifically in senescent cells while sparing healthy cells.

Is FOXO4-DRI FDA approved?

No, FOXO4-DRI is not currently FDA approved. Current status: Preclinical - Extensive animal research, no human trials initiated yet

What are the side effects of FOXO4-DRI?

Reported side effects include: Generally well-tolerated in animal studies, Injection site reactions (burning, itching), Fatigue, Muscle soreness, Nausea. Individual responses vary based on dosage, duration, and personal health factors.

What is the typical dose of FOXO4-DRI?

Community-reported common dose: 2-10 mg every other day for 3 doses (one cycle) (3 doses every other day, 1-3 cycles per year). Range: 2-25 mg per injection, 6-75 mg total per cycle. Administration: Subcutaneous injection (community), IV/IP in animal studies. Community-reported doses from biohacker protocols. No human clinical trials completed. Not medical advice. Consult healthcare provider.

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